Member, Whitehead Institute
Daniel K. Ludwig and American Cancer Society Professor of Biology
Massachusetts Institute of Technology
Dr. Weinberg’s work has been focused on a small group of cells called stem cells that are present in both normal mammary tissue as well as in breast cancers. Stem cells (SCs) are cells that can make more of themselves and, in addition, can generate cells that have taken on the specialized traits of the tissue in question. Cancer stem cells represent a minority population that, unlike most of the cells in the tumor, are able to spawn new tumors in other tissues, a process called metastasis. In addition, the cancer stem cells are highly resistant to various therapeutic treatments, leading to tumor progression or recurrence. The elimination of cancer stem cells in breast cancer will be critical for durable clinical responses if not cures, given the roles of these cells in spawning clinical relapses.
Dr. Weinberg’s team has been examining the origin of the cancer stem cells in experimental models of breast cancers and found that the normal stem cells in the milk ducts are found in the basal cell layer–away from the cavity of the milk ducts--whereas tumors arise in the luminal cell layer, which directly faces the cavity of the ducts. This observation proves for the first time that the cancer stem cells do not derive from normal mammary stem cells. This finding has important implications for the development of anti-breast cancer therapies that are designed to target and eliminate the cancer stem cells. Because the cancer stem cells have a distinctly different origin from normal mammary stem cells, it now plausible to target the cancer stem cells selectively without inflicting damage on the normal stem cells. In the coming year, Dr. Weinberg will continue his work in this area and conduct studies to further characterize how cancer stem cells promote metastasis.
Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research and the Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology (MIT). He is also the first Director of the Ludwig Cancer Center at MIT. He is an internationally recognized authority on the genetic basis of human cancer. Dr. Weinberg and his colleagues isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene. The principal goal of his research program is to determine how oncogenes, their normal counterparts (proto-oncogenes), and tumor suppressor genes fit together in the complex circuitry that controls cell growth. More recently, his group has succeeded in creating the first genetically defined human cancer cells. He is particularly interested in applying this knowledge to improve the diagnosis and treatment of breast cancer.